Symmetrel: Adjunctive Management for Parkinson's and Influenza A - Evidence-Based Review
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Amantadine hydrochloride, sold under the brand name Symmetrel among others, is a medication with a fascinating dual history. Initially developed as an antiviral agent, its unexpected efficacy in Parkinson’s disease reshaped its clinical trajectory. It functions as both an antiviral, primarily against influenza A, and as an antiparkinsonian agent. Its mechanism in Parkinson’s is distinct from other medications, offering a unique therapeutic option, particularly for managing dyskinesias associated with long-term levodopa use. Its role has evolved, but it remains a valuable tool in specific neurological and infectious disease contexts.
1. Introduction: What is Symmetrel? Its Role in Modern Medicine
Symmetrel, with the active ingredient amantadine hydrochloride, is a synthetic tricyclic amine. It occupies a unique niche. For healthcare professionals, what is Symmetrel used for spans two primary domains: the management of Parkinson’s disease and the prophylaxis/treatment of influenza A virus infections. Its discovery and application highlight a classic case of drug repurposing. After its initial approval as an antiviral, clinicians observed its serendipitous benefits for parkinsonian symptoms, leading to its formal indication. Today, while newer agents exist, Symmetrel is often considered for its specific ability to reduce levodopa-induced dyskinesia, a challenging side effect of primary Parkinson’s therapy. Its medical applications provide a complementary approach rather than a first-line monotherapy.
2. Key Components and Bioavailability of Symmetrel
The composition of Symmetrel is centered on its single active pharmaceutical ingredient: amantadine hydrochloride. It is not a complex botanical extract but a defined chemical entity.
- Active Ingredient: Amantadine Hydrochloride (C10H17N•HCl).
- Standard Release Form: It is commercially available in 100 mg capsules and a syrup formulation (50 mg/5 mL). An extended-release formulation (Gocovri®) is also available, which is specifically indicated for dyskinesia in Parkinson’s disease patients receiving levodopa.
Regarding bioavailability, amantadine is well-absorbed from the gastrointestinal tract after oral administration. Nearly the entire dose is absorbed, with peak plasma concentrations occurring approximately 2-4 hours after a single dose. Its bioavailability is not significantly enhanced by food, though administration with food can sometimes mitigate minor gastrointestinal upset. The drug is not extensively metabolized in the liver; about 90% of a dose is excreted unchanged in the urine via glomerular filtration and tubular secretion. This renal clearance is a critical factor in dosing, necessitating adjustment in patients with impaired kidney function to prevent accumulation and toxicity.
3. Mechanism of Action of Symmetrel: Scientific Substantiation
Understanding how Symmetrel works requires examining its two distinct mechanisms.
For its antiparkinsonian effects, the primary mechanism of action is believed to be the antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors. In Parkinson’s disease, there’s a complex imbalance between dopamine and glutamate in the basal ganglia. By blocking NMDA receptors, Symmetrel reduces the excitatory effects of glutamate, which can become overactive as a compensatory mechanism in dopamine deficiency. This action helps to re-stabilize neuronal circuitry. Additionally, it has weak anticholinergic properties and may promote the release of dopamine from stored sites and inhibit its reuptake, though these are considered secondary effects. The NMDA antagonism is particularly relevant for its effect on dyskinesia, as it is thought to modulate the abnormal signaling pathways that lead to these involuntary movements.
For its antiviral effects, the mechanism involves interfering with the viral M2 protein, an ion channel. For influenza A viruses, this protein is crucial for uncoating the virus once it enters the host cell. By blocking the M2 channel, Symmetrel prevents the acid-mediated dissociation of the viral ribonucleoprotein complex, thereby halting viral replication at an early stage. It’s important to note that this mechanism is specific to influenza A viruses; it is not effective against influenza B, which lacks the M2 protein.
4. Indications for Use: What is Symmetrel Effective For?
The indications for Symmetrel are well-defined, based on decades of clinical use and regulatory approval.
Symmetrel for Parkinson’s Disease
It is used for the treatment of idiopathic Parkinson’s disease (Paralysis Agitans), post-encephalitic parkinsonism, and drug-induced extrapyramidal reactions. It is effective in relieving symptoms like akinesia, rigidity, and tremor. Its most valued modern application is as an adjunct to levodopa/carbidopa therapy to smooth out the “on-off” phenomenon and, more notably, to reduce the severity of levodopa-induced dyskinesias.
Symmetrel for Influenza A Prophylaxis and Treatment
It is indicated for the prophylaxis and symptomatic management of respiratory tract illnesses caused by influenza A virus strains. It can be used in both adults and children over the age of 1 year. However, widespread resistance in circulating influenza A strains has significantly limited its utility for this indication in recent years, and it is no longer a first-line recommendation by major public health bodies like the CDC.
Symmetrel for Fatigue in Multiple Sclerosis
This is a common off-label use. Some patients with MS report a subjective improvement in feelings of lassitude and fatigue with low-dose amantadine, though the evidence base is less robust than for its approved indications.
5. Instructions for Use: Dosage and Course of Administration
Clear instructions for use are vital for safety and efficacy. The dosage varies significantly by indication and patient population.
| Indication | Patient Group | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Parkinson’s Disease | Adults | 100 mg once or twice daily. | May increase to 400 mg/day in divided doses if necessary. | Start low, go slow. Often given with levodopa. |
| Influenza A Prophylaxis | Adults & Children (≥10 yrs) | 200 mg once daily OR 100 mg twice daily. | Once daily for 1-2 days, then once or twice daily for the duration of exposure. | Course of administration is typically 10-14 days. |
| Influenza A Prophylaxis | Children (1-9 yrs) | 4.4-8.8 mg/kg/day. | Once or twice daily, not to exceed 150 mg/day. | Use weight-based dosing. Syrup formulation is preferred. |
| Influenza A Treatment | Adults | 200 mg as a single dose OR 100 mg twice daily. | Initiate within 24-48 hours of symptom onset and continue for 24-48 hours after symptoms disappear. | |
| Renal Impairment | CrCl 30-50 mL/min | 200 mg for first dose, then 100 mg daily. | Once daily. | Dosage adjustment is mandatory. |
| Renal Impairment | CrCl 15-29 mL/min | 200 mg for first dose, then 100 mg every other day. | Every other day. | |
| Renal Impairment | CrCl <15 mL/min | 200 mg every 7 days. | Once weekly. |
How to take: Can be taken with or without food. If GI upset occurs, administer with meals.
6. Contraindications and Drug Interactions with Symmetrel
A thorough review of contraindications and potential drug interactions is essential prior to prescribing.
Contraindications:
- Known hypersensitivity to amantadine hydrochloride or any component of the formulation.
- Severe renal impairment (end-stage renal disease) without appropriate, supervised dosing.
Important Drug Interactions:
- Anticholinergic Agents (e.g., benztropine, trihexyphenidyl): Concurrent use can potentiate anticholinergic side effects like dry mouth, blurred vision, urinary retention, and constipation. We once had a patient, Mr. Henderson, on trihexyphenidyl who started amantadine and presented with acute urinary retention—a classic and unpleasant lesson in additive effects.
- CNS Stimulants: May increase the risk of insomnia, nervousness, and potential cardiovascular effects like tachycardia.
- Drugs Eliminated by Renal Tubular Secretion (e.g., cimetidine, quinidine, ranitidine): These can compete for excretion and potentially increase amantadine plasma levels, increasing the risk of toxicity.
- Alcohol: Should be avoided as it may increase the risk of CNS effects such as dizziness, lightheadedness, and confusion.
Special Populations:
- Pregnancy: Category C. Use only if the potential benefit justifies the potential risk to the fetus. Is it safe during pregnancy? The answer is that it should be used with caution and only when clearly needed.
- Lactation: Amantadine is excreted in breast milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug.
7. Clinical Studies and Evidence Base for Symmetrel
The clinical studies and scientific evidence for amantadine are extensive, though many key trials date back several decades.
For Parkinson’s disease, a landmark study published in JAMA demonstrated its efficacy in reducing parkinsonian symptoms. More recent and relevant clinical studies have focused on its role in managing levodopa-induced dyskinesia (LID). A meta-analysis in Cochrane Database of Systematic Reviews concluded that amantadine is an effective treatment for LID, with a significant reduction in dyskinesia scores compared to placebo. The development of the extended-release formulation was specifically driven by the need to maintain stable plasma levels to manage LID throughout the day, with pivotal trials showing a >50% reduction in dyskinesia in a significant portion of patients.
For its antiviral use, early scientific evidence from the 1960s and 70s established its efficacy in preventing and treating influenza A. However, surveillance data over the past two decades has shown a dramatic increase in resistance. The CDC’s annual reports consistently indicate high levels of resistance among circulating influenza A (H3N2) and 2009 pandemic H1N1 viruses, rendering the drug ineffective for these strains and removing it from standard treatment guidelines.
8. Comparing Symmetrel with Similar Products and Choosing a Quality Product
When patients or clinicians ask about Symmetrel similar agents or which antiparkinsonian drug is better, context is everything.
- vs. Levodopa: Symmetrel is far less potent for treating the core motor symptoms of Parkinson’s. It is not a replacement but an adjunct. Its value lies in its different mechanism of action, as discussed earlier, making it useful for managing side effects of levodopa itself.
- vs. Dopamine Agonists (e.g., pramipexole, ropinirole): Agonists directly stimulate dopamine receptors. Amantadine’s NMDA antagonism offers a non-dopaminergic pathway, which can be beneficial when dopamine-related side effects like hallucinations or impulse control disorders are a concern.
- vs. Other Antivirals (e.g., Oseltamivir/Tamiflu): This is a clear-cut case. Due to widespread resistance, neuraminidase inhibitors like oseltamivir are the preferred choice for influenza. Symmetrel is rarely indicated for this purpose anymore.
How to choose a quality product: For a branded drug like Symmetrel, the product is standardized. The main consideration is ensuring the medication is sourced from a legitimate pharmacy to avoid counterfeits. For the generic amantadine, it’s manufactured by several reputable companies under strict FDA regulations, so bioequivalence is assured.
9. Frequently Asked Questions (FAQ) about Symmetrel
What is the recommended course of Symmetrel to achieve results for Parkinson’s?
For Parkinson’s, it’s a chronic therapy. Benefits may be seen within 48 hours, but the full effect can take a few weeks. The course of administration is ongoing, and the dose is titrated for effect and tolerability.
Can Symmetrel be combined with antidepressants like SSRIs?
Yes, it can be, but with monitoring. There is a potential for pharmacodynamic interaction, as both can affect serotonin levels, though the risk of serotonin syndrome is considered low. The bigger issue is that both can cause CNS effects like dizziness, so patients should be cautioned about additive sedation.
Why is monitoring for livedo reticularis important?
Livedo reticularis, a purplish, net-like skin discoloration, is a common and usually benign side effect of amantadine. However, its appearance can be a marker of long-term use and accumulation. While not dangerous itself, it prompts us to re-evaluate the continued need for the drug and check for other signs of toxicity.
Does Symmetrel cause cognitive issues?
It can, particularly in the elderly or those with pre-existing cognitive impairment. Confusion, hallucinations, and nightmares are known side effects. This is a key reason we start with a low dose and titrate slowly.
10. Conclusion: Validity of Symmetrel Use in Clinical Practice
In conclusion, the risk-benefit profile of Symmetrel remains favorable for its specific neurological indications. While its role in antiviral therapy has been largely superseded, its utility as an adjunctive treatment in Parkinson’s disease, particularly for the management of levodopa-induced dyskinesia, secures its place in the therapeutic arsenal. Its unique mechanism of action provides a valuable non-dopaminergic option. The key to its safe use lies in careful patient selection, vigilant monitoring for CNS and renal side effects, and appropriate dose adjustment. For the right patient, Symmetrel is a valid and effective component of a comprehensive management plan.
You know, I was going through some old charts the other day and came across Eleanor, a woman I started on amantadine back in, must have been 2010. She was in her late 60s, lovely person, but her life was being ruled by these wild, flailing dyskinesias from her Sinemet. She was embarrassed to go out. We’d tried adjusting her levodopa timing, but it was a trade-off—less dyskinesia but more “off” time, she was miserable. I remember the conversation with her neurologist; he was skeptical, thought amantadine was a bit “old hat” and wasn’t convinced the benefit would outweigh the side effect risk, especially given her age. We had a bit of a professional disagreement, but he trusted my judgment on the ground.
So we started her on 100 mg daily. The first week, nothing. Then she reported a slight “dulling” of the movements. No livedo, no confusion, which was a relief. We bumped it to 100 mg BID after a month. It wasn’t a miracle, let’s be clear. But it took the edge off. The flailing became a sway. She told me she felt she had a bit of her dignity back, that she could have a cup of tea without wearing half of it. That was the real-world outcome no trial could fully capture.
The interesting, almost failed insight was with another patient, David. He had pretty significant renal impairment we’d missed on his initial workup. Started him on a standard 100 mg BID and within ten days his family was calling, saying he was seeing “little people” in the corners of the room and was profoundly confused. That was a tough lesson—our fault for not checking his CrCl thoroughly. We stopped the drug, his creatinine was elevated, and it took nearly a week for him to clear the amantadine and return to baseline. It hammered home the renal clearance issue in a way the textbook never did. You get complacent with drugs you’ve used for years.
I followed Eleanor for another three years before she moved to be closer to her daughter. The effect held steady. She’d occasionally get the livedo on her legs in the winter, but it never bothered her. “A small price to pay,” she’d say. Her testimonial was simple: “It gave me my afternoons back.” That’s the longitudinal follow-up that matters. It’s not the blockbuster drug it once was, but in the nuanced, complicated world of Parkinson’s care, it’s a tool that still has a sharp edge if you know how and when to use it.